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Although various strategies have been included in nanotoxicity evaluation, epitranscriptomics has rarely been integrated into this field. In this proof-of-concept study, N6-methyladenosine (m 6 A) changes of mRNA in HEK293T cells induced by three bovine serum albumin (BSA)-templated Au, CuS and Gd 2 O 3  nanoparticles are systematically explored, and their possible biological mechanisms are preliminarily investigated. It has been found that all the three BSA-templated nanoparticles can reduce m 6 A levels, and the genes with reduced m 6 A are enriched for TGF-beta signaling, which is critical for cell proliferation, differentiation and apoptosis. Further results indicate that abnormal aggregation of m 6 A-related enzymes at least partly account for the nanoparticle-induced epitranscriptomic changes. These findings demonstrate that epitranscriptomics analysis can provide an unprecedented landscape of the biological effect induced by nanomaterials, which should be involved in the nanotoxicity evaluation to promote the potential clinical translation of nanomaterials.

RNA m6A Alterations Induced by Biomineralization Nanoparticles: A Proof-of-Concept Study of Epitranscriptomics for Nanotoxicity Evaluation